Amino acids protect epithelial cells from local toxicity by absorption enhancer, sodium laurate

To develop the safe absorption-enhancing formulation attenuating the local toxicity caused by an absorption enhancer, sodium laurate (C12), the effect s of amino acids on the local toxicity by C12 were examined in rats. The ab sorption of phenol red, an unabsorbable marker drug, was significantly enha nced by 10 mM C12 in an in situ colon loop study and the addition Of L-glut amine (L-Gln), L-arginine, or L-methionine at 10 mM did not change the prom oting effect of C12. However, C12 significantly increased the elution of ph ospholipids, total protein, and lactate dehydrogenase, which are markers fo r local toxicity, from colon, but these amino acids attenuated the local to xicity caused-by C12 significantly. Transport study using an Ussing-type ch amber showed that the permeability of colonic membrane to phenol red was si gnificantly enhanced by C12 and that L-Gln did not decrease the permeabilit y enhanced by C12. Transmucosal electrical resistance was extensively decre ased by C12, indicating that C12 could enhance the drug absorption at least partly by expanding the paracellular route. L-Gln significantly, but not c ompletely, recovered resistance lowered by C12. Electrical potential differ ence was markedly reduced by C12, suggesting that C12 lowered the viability of mucosal cells, but 10 MM L-Gln significantly recovered potential differ ence almost to the control level. These results suggested the possibility t hat absorption-enhancing formulation with low local toxicity, which is low enough to be used practically, could be developed by using an amino acid li ke L-Gln as an ingredient attenuating the local toxicity caused by C12. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.